Ask about this productRelated genes to: FGF18 protein
- Gene:
- FGF18 NIH gene
- Name:
- fibroblast growth factor 18
- Previous symbol:
- -
- Synonyms:
- FGF-18, ZFGF5
- Chromosome:
- 5q35.1
- Locus Type:
- gene with protein product
- Date approved:
- 1998-12-22
- Date modifiied:
- 2016-10-05
Related products to: FGF18 protein
Related articles to: FGF18 protein
- While clinical trials of human pluripotent stem cell-derived midbrain dopamine (mDA) neuron precursor grafts for Parkinson's disease (PD) are ongoing, current protocols remain suboptimal. In particular, the yield of TH+ mDA neurons after in vivo grafting and the expression of certain mDA neuron and subtype-specific markers require improvement. Single-cell transcriptomic analyses of grafts have revealed low proportions of mDA neurons and substantial off-target contamination. Here, we present an optimized mDA neuron differentiation strategy that builds on our clinical-grade ("Boost") protocol by adding FGF18 and IWP2 treatment ("Boost+") at the neurogenesis stage. Boost+ mDA neurons show higher expression of EN1, PITX3, and ALDH1A1. Improvements in mDA neuron yield and transcriptional similarity to primary mDA neurons are observed in vitro and following transplantation. Single-nucleus RNA sequencing demonstrates enrichment of A9 mDA neurons within Boost+ grafts. Functional studies in vitro demonstrate increased dopamine production and release and improved electrophysiological properties. In vivo analyses show higher percentages of TH+ mDA neurons, resulting in efficient rescue of amphetamine-induced rotation behavior in the 6-OHDA rat model and rescue of deficits in some nondrug-induced assays, including the ladder rung assay, which are not improved by Boost mDA neurons. The Boost+ conditions present an optimized differentiation protocol with advantages for disease modeling and mDA neuron grafting paradigms. - Source: PubMed
Publication date: 2026/05/15
Kim Tae WanPiao JinghuaBocchi Vittoria DKoo So YeonChoi Se JoonChaudhry FayzanYang DongheCho Hyein SHergenreder EmilianoRuiz Perera LuciaJoshi SubhashiniAbou Mrad ZakiClaros NidiaDonohue Shkurte AdemiEun Im YeongJeong Hyo JaeFrank Anika KWalsh Ryan MMosharov Eugene VBetel DoronTabar VivianeStuder Lorenz - Hereditary Multiple Osteochondromas (HMO) is a rare, pediatric disease characterized by osteochondromas that form next to the growth plates, accumulate over time and cause major health problems. Most HMO cases are linked to loss-of-function mutations in Golgi-resident proteins EXT1 or EXT2, but tumor development remains unclear. In particular, the source of tumor-forming progenitors has long been debated, with recent studies pointing to a perichondrial origin. Perichondrium normally flanks the growth plates, has essential roles in skeletal growth, and is composed of an inner cuboidal cell layer and an outer fibroblastic cell layer. Here, we set out to determine by genetic approaches whether the tumors do in fact derive from perichondrium and if one or both layers provide progenitors. We employed Pdgfrα-CreER and Fgf18-CreER transgenic mice that respectively, target inner and outer layers or the outer layer only. Mice were mated with floxed Ext1 mice to conditionally ablate the causative gene, mimicking tumor induction in patients. Compound juvenile Pdgfrα-CreER;Ext1 and Fgf18-CreER;Ext1 mice were injected with tamoxifen and monitored for tumor development over time. By 4-8 weeks post-tamoxifen, osteochondromas had formed in Pdgfrα;Ext1 mutants targeting both layers, but none were appreciable in Fgf18;Ext1 mutants targeting the outer layer, based on μCT scans, histochemistry and td-Tomato cell lineage tracing. In situ analyses verified that Ext1 had been ablated in the outer layer of Fgf18;Ext1 mutants. Analyses also showed that the developing osteochondromas in the Pdgfrα;Ext1 mutants displayed strong expression of cartilage proteins and abundant pSMAD1 and pSMAD2 proteins that mediate pro-chondrogenic BMP/TGFβ signals. The data provide new evidence that perichondrium progenitors, and more specifically inner layer cells delineated by Pdgfrα expression, initiate osteochondroma formation, being redirected into an ectopic chondrogenic program by Ext1 loss and deficiency of its vital function. - Source: PubMed
Publication date: 2026/05/01
Mundy ChristinaRamesh SadhanaCatheline Sarah ESaunders CheriKoyama EikiPacifici Maurizio - Musculoskeletal disorders and injuries are highly prevalent and encompass a broad range of conditions, including bone fractures and segmental defects, tendinopathies and tendon injury, and cartilage disorders such as osteoarthritis, cartilage defects, and intervertebral disc disease. These conditions can arise from diverse causes including trauma and injury, tumor resection, congenital abnormalities, and age-related degeneration. In the past decades, administration of chemically modified mRNA (cmRNA) encoding growth factors and transcriptional regulators has demonstrated effectiveness in repairing musculoskeletal tissues in preclinical studies. This review summarizes recent advancements in bone, tendon, cartilage, intervertebral disc, and muscle regeneration achieved through the localized delivery of protein-encoding mRNAs to express therapeutic target proteins. Delivery of cmRNA encoding growth factors such as BMP-2, BMP-9, VEGF, FGF-18, and IGF-1, or transcriptional regulators including Runx1, to various animal models has shown beneficial effects on bone, tendon, cartilage, and muscle injury repair in preclinical models. Alongside these progresses, the advantages and disadvantages of applying chemically modified mRNA for musculoskeletal tissue regeneration are also discussed. While studies show the promise of cmRNA for therapeutic applications in orthopedic tissue regeneration, more research is required to optimize growth factors and delivery methods, as well as validate long-term safety and efficacy prior to successful translation into new therapies to benefit patients. - Source: PubMed
Publication date: 2026/04/01
Force Britney SGao XueqinHuard Johnny - Tendons are specialized connective tissues with limited intrinsic healing properties due to hypovascularity and low metabolic activity. Mesenchymal stem cells (MSCs) possess regenerative potential for tendon injuries. Among the diverse sources of MSCs, those derived from the bone marrow (BM-MSCs) and adipose tissue (AD-MSCs) are the leading candidates. However, their relative efficacy remains underexplored, particularly in terms of biological characteristics and tenogenic differentiation. In addition, the signaling pathways driving tenogenic differentiation processes remain poorly understood. This study aimed to comprehensively investigate the regenerative potential of AD-MSCs and BM-MSCs for tendon repair. - Source: PubMed
Publication date: 2026/04/09
Khaled HadeerZayed MohammedKim BumseokJeong Byung-HoonOh Sang-Ik - Dysregulated expression of tight junction proteins and compromise of blood-brain barrier (BBB) integrity are associated with pathological progression of HIV-1-associated neurocognitive disorders (HAND). Fibroblast growth factor-18 (FGF18), an important member of the fibroblast growth factor (FGF) family, has been considered a neuroprotectant with a wide range of physiological functions. However, the effects of FGF18 in HAND have not been reported previously. Here, we report that FGF18 expression was reduced in the cortex of mice challenged with HIV-1 Tat. Intracerebroventricular administration of FGF18 suppressed vascular inflammation in the cortex of HIV-1 Tat-challenged mice by inhibiting VCAM-1 and ICAM-1 expression. FGF18 alleviated BBB dysfunction induced by HIV-1 Tat through upregulating ZO-1 expression. Mechanistically, FGF18 prevented HIV-1 Tat-induced downregulation of Wnt-3a and β-catenin. We further demonstrate that FGF18 ameliorated HIV-1 Tat-induced cytotoxicity in bEnd.3 brain microvascular endothelial cells by reducing LDH and HMGB-1 release. Moreover, FGF18 protected the endothelial permeability of bEnd.3 cells and restored trans-endothelial electrical resistance (TEER) in cells challenged with HIV-1 Tat. Consistently, FGF18 prevented the reduction of ZO-1 expression as well as Wnt-3a/β-catenin levels in bEnd.3 cells challenged with HIV-1 Tat. Importantly, silencing of Wnt-3a abrogated the beneficial effects of FGF18 in increasing ZO-1 expression and reducing endothelial permeability, indicating that the protective effects of FGF18 are mediated by Wnt-3a/β-catenin signaling. We conclude that FGF18 may serve as an effective neuroprotective agent for the treatment of HAND. - Source: PubMed
Zhang PengfeiWei SongFu FanyuGu HaoYang Ye